Background

Uterine leiomyomas are among the most common problems encountered by the obstetrician/gynecologist. They are a frequent cause of pelvic pain and abnormal uterine bleeding and are thought to be involved in infertility. Uterine leiomyomas are the most frequent indication for hysterectomy in the United States. Many patients with symptomatic leiomyomas desire to retain the option of future childbearing or simply want to preserve their uterus. For these women, myomectomy, the removal of the myomas with reconstruction and preservation of the uterus, is an important option.

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History of the Procedure

Successful abdominal myomectomy was reported as early as 1845 by brothers Washington and John Atlee in the American Journal of Medical Science. Washington, the older brother, eventually published his experience with 14 abdominal myomectomies, winning the annual essay award of the American Medical Association despite the death of 5 of the patients.
[1]

The operation was slow to gain widespread use. In 1875, W.H. Byford gave the Chairman's address to the American Medical Association Section on Obstetrics and Gynecology and said abdominal myomectomy was "so dangerous and difficult as not to be thought of except in desperate conditions."
[1]

At the turn of the 20th century, abdominal myomectomy was associated with a mortality rate of 40%, compared with 6-7% for abdominal hysterectomy. Victor Bonney is credited for advocating and popularizing the procedure in the 1920s.
[2]

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Problem

Uterine leiomyomata, or fibroids as they are more frequently known, affect more than 20% of reproductive-aged women
[3] . Patients can have a single myoma or numerous myomas. They are benign muscular growths in the wall of the uterus (figure1). The majority of myomas are small, do not cause symptoms, and are noted as incidental findings during routine pelvic examinations or pelvic imaging studies. When they enlarge, they can cause a mass effect, resulting in pelvic pressure or pain or a distortion of the uterine wall or endometrial cavity, which leads to abnormal uterine bleeding. More infrequently, myomas can prolapse through the cervix or may be confused for an ovarian mass. They can also cause problems in pregnancy depending upon their location and, in some patients, myomas are thought to be linked to infertility.

Epidemiology

Frequency

Uterine leiomyomata occur in 20-40% of reproductive-aged women.
[3] Results from some ultrasonographic studies indicate the presence of at least one small myoma in 51% of pre-menopausal women. Of these women, 10-35% of Caucasian women and 30-50% of African American women have fibroids of clinical significance.
[4] Myomas grow in response to estrogen stimulation and regress after menopause. Thus, they are most frequently found in women in their fifth decade of life and are quite rare in those younger than 20 years. In 2001, Schwartz reviewed the epidemiology of leiomyomas. The risk is 2-3 times higher in African American women than in white women, increases with age, decreases with having a live-born child, may increase with body mass index, and may decrease with cigarette smoking. Riskmayalso increase with diets high in red meat and ham and it may decrease with diets high in intake of green vegetables.
[5]

Although most myomas are asymptomatic, there are many women who have significant symptoms from myomas, and myomas are the most frequent indication for hysterectomy in the United States. This indication constituted 38.1% of all hysterectomies (1.36 million) from 1994-1999.
[6] Figures for myomectomy are older, but, in 1984, 18,000 myomectomies were performed, compared with 112,000 hysterectomies, suggesting approximately 1 myomectomy per 6 hysterectomies among women aged 15-44 years.
[7] The symptoms of fibroids, along with both surgical and medical treatments, result in enormous costs for affected women and society. A study designed to estimate the annual cost of various methods of treatment of uterine fibroids showed that the mean cost for a myomectomy in the United States was $6,707 compared to $6,331 for abdominal hysterectomy, $7,108 for laparoscopicallyassistedvaginal hysterectomy, $6,809 for supracervical hysterectomy. Length of hospitalization was similar between totalabdominalhysterectomy(mean 2.9 days), supracervical hysterectomy (mean 2.7 days) and Myomectomy 2.6 days).
[8]

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Etiology

Leiomyomas are smooth muscle tumors that form in the uterine wall. The development and growth of uterine fibroids are influenced by multiple factors including autocrine and paracrine growth factors, genetic abnormalities, race, and environmental estrogen exposure related to age of menarche, obesity, and parity.
[9]

The precise etiology is not known, although many cytogenetic and genetic studies have been performed. Approximately 40-50% of myomas have karyotypic abnormalities, particularly involving chromosomes 6, 7, 12, and 14. Within a myoma, all cells are identical and a monoclonal origin has been confirmed
[10] Other changes associated with the presence of myomas include increased expression of estrogen, progesterone, and insulin-like growth factor 1 and 2 receptors and abnormalities in the myometrium adjacent to the myoma.
[11]

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Pathophysiology

Although myomas are common, relatively few actually cause symptoms. Whether symptoms are present depends largely on a combination of size, number, and location of the myomas. In general, myoma growth is a result of the stimulation of estrogen, which is present until menopause. Over time, previously asymptomatic myomas may grow and become symptomatic. Conversely, many myomas begin to shrink as menopause removes the estrogen stimulation and many myoma-related symptoms resolve spontaneously shortly after menopause.

Myomas are generally categorized by location. Intramural myomas are entirely or mostly contained within the myometrium (Figure2). Subserosal myomas project outward from the uterus (Figure 3). Submucosal myomas project into the endometrial cavity (figure 4). Pedunculated myomas are attached to the uterine wall by stalks and can be directed into either the peritoneal or the uterine cavity (figure 5).

Pelvic pressure and pain symptoms are usually the result of mass effect. This can occur either from a single large myoma or from a combination of multiple smaller myomas. A fibroid uterus can grow to be quite large, at times reaching the size of a term gravid uterus. Interestingly, perhaps due to the slow growth and accommodation by the patient, some extremely large uteri are well tolerated by patients and do not require intervention. Some large myomas that impinge on the ureters can cause hydronephrosis and, very rarely, ureteral obstruction.

Bleeding abnormalities related to myomas are usually the result of distortion of the endometrial cavity. Unlike pain, which is usually caused by large or multiple myomas, some patients have significant bleeding from a single, small, strategically placed myoma. A submucosal myoma can prolapse through the cervix and may cause no symptoms or may cause significant bleeding or pain.

Acute pain resulting from myomas is uncommon and usually stems from one of two possibilities. Pedunculated myomas can undergo torsion, causing the same severe pain as torsion of the ovary. Large myomas can outgrow their blood supply, leading to infarction and necrosis (degenerating myoma), which can be extremely painful. Lastly, prolapse of a myoma can be acutely painful.

Although general agreement is lacking on the mechanism, myomas are also thought to be related to infertility, fetal malpresentations, and preterm labor. Possible mechanisms for infertility include distortion of the endometrial cavity and abnormal endometrial surface, thereby affecting both sperm transport and embryo implantation.

Very rarely, myomas can be associated with erythrocytosis. This triad of myomatous uterus, erythrocytosis, and maintenance of normal hematologic values despite menorrhagia is called myomatous erythrocytosis syndrome.
[10] A number of etiologies have been hypothesized, but alterations in erythropoietin levels seem likely.

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Presentation

Most leiomyomata are small and do not cause symptoms. Many are found as incidental findings after an obstetric or gynecologic ultrasonographic examination (Figure 6) or after a routine pelvic examination.

However, myomas can cause a number of symptoms. They can cause menstrual irregularities, particularly menorrhagia. This bleeding usually begins gradually and progressively worsens as the responsible myoma enlarges. A regular menstrual pattern should be still discernible despite the development of heavier or prolonged bleeding. If no regular pattern is noted, an alternative etiology such as chronic anovulation is more likely.

Some patients present with progressive pelvic pressure, pelvic pain, or low back pain. The differential diagnoses for such symptoms is diverse; however, if they are noted in someone with a medium- or large-sized uterus (>14-15 weeks' size), the myomas are more likely to be contributing. Some fibroid uteri can grow out of the pelvis and into the abdomen, where they can be palpated by the patient. This can be disturbing, even if the patient is having mild or no symptoms. Some are visible, distorting the abdominal wall and, at times, making the patient appear pregnant.

Most myomas grow slowly, and some remain relatively unchanged over prolonged periods. In the past, rapid growth was considered worrisome for leiomyosarcoma. In 1994, Parker et al showed that sarcoma was quite rare, even in rapidly growing uteri (0.27%). This risk was similar to the risk of leiomyosarcoma in myomas that were stable in size (0.21%).
[14] However, most of the patients were premenopausal. Rapid growth in postmenopausal women should be treated with greater caution.

The diagnosis of a degenerating myoma should be considered in a patient with known fibroids and an acute onset of severe pelvic pain. The patient can also develop fever and an elevated white blood cell count that can be confused with infection. Upon examination, tenderness is usually quite specific and localized to the exact region of the degenerating myoma.

Infertility evaluations usually include an investigation for myomas, specifically submucosal myomas. Ultrasonography, hysterosalpingography (HSG), sonohysterography, or hysteroscopy are used frequently because submucosal myomas may not be detectable during pelvic examination.

Although less common, myomas can be found incidentally on speculum examination when they prolapse through the cervical os. Prolapsing myomas can also present with acute pain caused by “delivery” of the myoma through the cervix. Pedunculated myomas can also be mistaken for adnexal masses on routine pelvic examination.

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Indications

The decision to perform surgery for uterine leiomyomata is complex and varies from patient to patient based on their medical comorbidities, surgical history, clinical scenario and patient preference. In general, consideration for a hysterectomy is given in patient with:

Chronic lower abdominal pain or low back or pelvic pressure with evidence of sizeable leiomyoma on imaging studies

Leiomyomata that are palpable abdominally

Indications for myomectomy are similar and this procedure is considered when patient either has a desire for future fertility or feels strongly about retaining their uterus. Whether discussing hysterectomy or myomectomy, these criteria are directed at relieving symptoms or improving quality of life by decreasing the patient's concerns. No indications exist for removing asymptomatic fibroids

A definite risk exists for myoma recurrence after myomectomy and, with it, the need for a repeat surgical procedure in the future. If the patient no longer desires to retain her fertility or her uterus, hysterectomy is the usual procedure of choice. Interestingly, a number of women who have completed childbearing still request myomectomy for management of symptomatic myoma. This decision is usually motivated by patient preference and a desire to retain organs. Because the short-term risks of myomectomy compare favorably with hysterectomy
[11] and despite the risk of recurrence, a myomectomy is not unreasonable for appropriately counseled patients.

Although controversial, myomectomies are also performed for patients with infertility in the presence of uterine fibroids. Several studies suggest that patients with fibroids who are undergoing assisted reproductive technology procedures may have lower success rates compared with patients without fibroids.
[12, 13] On the other hand, a Cochrane review on surgical management of fibroids in infertile patients did not find any statistically significant difference in clinical pregnancy rate, miscarriage rate or live birth rate between patients with uterine fibroids who had myomectomies and those who were managed conservatively. The authors caution that this data must be interpreted carefully because of the small nature of the existing studies and the significant need for additional data on the topic.
[14] Further, there is no randomized data regardingtheimpact of hysteroscopic myomectomy of fertility outcomes butseveral case series report favorable pregnancy rates.
[15, 16] Current recommendations include consideration of myomectomy in infertile women after extensive evaluation eliminating other causes of infertility.

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Relevant Anatomy

Leiomyomata are usually confined to the myometrium but can occur in the lower uterine segment or cervix or can project out into the broad ligament. These myomas are frequently the most difficult to remove and are problematic during both hysterectomy and myomectomy.

Within the uterus, the myomas can be at any level within the uterine wall. Intramural myomas are entirely or mostly contained within the myometrium(Figure7). Subserosal myomas project outward from the uterus (Figure 8). Submucosal myomas project into the endometrial cavity (figure 9). Pedunculated myomas are attached to the uterine wall by stalks and can be directed into either the peritoneal or the uterine cavity (figure 10).

Contraindications

Myomectomy has a number of important contraindications. Myomectomy is not reasonable in the management of symptomatic leiomyomata in patients who no longer desire fertility or uterine preservation. It should not be performed if the possibility of endometrial cancer or uterine sarcoma have not been excluded. Generally, it should be avoided if the patient is pregnant. With the possible exception of otherwise unexplained infertility, it should not be performed in asymptomatic patients. No evidence supports prophylactic myomectomy of asymptomatic myomas for decreasing the risk of any adverse outcome later in life.

A relative contraindication to myomectomy is the strong possibility that a functional uterus could not be reconstructed after excision of the myomas. For myomectomy to be considered successful, reconstructing the uterus must be possible. Leiomyomata located in the region of the uterine vessels or broad ligament are sometimes difficult to remove without performing a hysterectomy. If the patient has numerous small myomas, removing them and reconstructing the uterus in such a way as to support a future pregnancy may be impossible. Excision of very large leiomyomata that constitute the entire anterior or posterior wall of the uterus may leave defects so large that closure is prohibited.

Robotic myomectomy. A 32-year-old woman was found to have a large fibroid during pregnancy. Postpartum, the fibroid caused pelvic pain and dyspareunia. Pelvic ultrasonography revealed a 10-cm fundal transmural fibroid. Part 1. Video courtesy of Tarek Bardawil, MD.

Robotic myomectomy. A 32-year-old woman was found to have a large fibroid during pregnancy. Postpartum, the fibroid caused pelvic pain and dyspareunia. Pelvic ultrasonography revealed a 10-cm fundal transmural fibroid. Part 2. Video courtesy of Tarek Bardawil, MD.

Disclosure: Received research grant from: Insigtec Inc<br/>Received consulting fee from Clinical Advisors Group for consulting; Received consulting fee from MEDA Corp Consulting for consulting; Received consulting fee from Gerson Lehrman Group Advisor for consulting; Received honoraria from ABOG for board membership.

Acknowledgements

Medscape Reference thanks Tarek Bardawil, MD, Assistant Professor, Department of Obstetrics and Gynecology, University of Miami Miller School of Medicine, for assistance with the video contribution to this article.